The production of blood cells such as erythrocytes (red blood cells), granulocytes, macrophages and lymphocytes is under the control of a set of protein molecules which stimulate multipotential precursor or stem cells in the bone marrow. During hematopoietic development, these multipotential cells form cells of limited developmental potential which are variously referred to as committed progenitor cells, colony forming cells or CFCs for individual blood cell types. Although there may be non-specific stimulators of the precursor stem cells or CFCs such as the so-called multi-CSF (interleukin-3) as described by Fung, M. C., et al., (Nature 307: 233-237(1984) or Yokota, T., et al., Proc. Nat'l. Acad. Sci. USA 81: 1070-1074 (1984)), there are specific regulators for each of the different cell lineages. In particular, the production of granulocytes and macrophages from their respective CFCs is under the control of glycoproteins such as granulocyte-macrophage colony stimulating factor (GM-CSF) as described by Burgess, A. W. et al., (J. Biol. Chem. 252: 1998-2003 (1977)), granulocyte colony stimulating factor (G-CSF) as described by Stanley, E. R. and Heard P. M., (J. Biol. Chem. 252: 4305-4312 (1977)) and macrophage colony stimulating factor (M-CSF) as described by Nicola, N. A. et al., (J. Biol. Chem. 258: 9017-9021 (1983)). Although these glycoproteins are of low abundance in the body, it has been possible to purify small amounts of the murine GM-CSF for partial amino acid sequence analysis and biological characterization.
However, unless an alternative source of these proteins can be found, these small amounts will be insufficient for clinical applications. If, however, these colony stimulating factors can be produced chemically or biosynthetically, it should be possible to use these factors to improve blood cell production in vivo, to produce blood cells in the laboratory for transfusion and to accelerate the maturation of leukemic cells. For each of these applications, it is imperative that the types of blood cells produced be restricted. In particular, it is important to limit the production or activation of lymphocytes and/or their precursors. Thus, whilst molecules such as multi-CSF could find application in some diseases where a general increase in blood cell production is required, the use of glycoproteins such as GM-CSF, G-CSF and M-CSF will be of particular importance since these stimulate only the production of cells required to fight primary infection or remove damaged tissue.